CN1662140A - Parasite control in animals - Google Patents

Abstract

The invention relates to the systemic and non-system control of parasites in animals by means of phenyl ketoenol derivatives.

Description

animal parasite control

The present invention relates to the use of phenyl ketone-enol derivatives for the systemic and non-systemic control of parasites in animals.

Phenylketone-enols are known compounds. These keto-enols are also known to possess pronounced insecticidal, acaricidal, herbicidal and fungicidal activities (EP-A-0528156, WO98/05638 and WO97/01535).

Surprisingly, it has now been found that certain phenylketo-enol derivatives are particularly suitable for the systemic and non-systemic control of parasites such as fleas, lice or flies in animals and in the environment.

These compounds are not necessarily suitable as arthropodicides in the veterinary field because of their activity with regard to developmental stages and egg fertility. Surprisingly, it was found that selected compounds are biologically active against relevant ectoparasites and hygiene pests when they are combined with certain application forms. The compounds are therefore particularly suitable for combating monohost tick species, lice and mites on domestic animals, for controlling stable flies, for example by feeding methods, and for controlling fleas, mites and ticks in pet breeding. This control effect can also be extended to resistant species.

The present invention relates to the use of phenyl ketone-enol derivatives of the general formula (I) and their enantiomerically pure forms for the preparation of medicaments for controlling parasites in animals and their environment:

in

X represents alkyl, halogen, alkoxy or haloalkyl,

Y represents hydrogen, alkyl, halogen, alkoxy, haloalkyl,

Z represents alkyl, halogen, alkoxy,

n represents a value from 0 to 3, or the groups X and Z together with the phenyl to which they are bonded form a naphthyl of the formula

where Y has the above meaning,

G represents hydrogen (a) or the following groups:

or E ⁺ (g)

A and B may be the same or different and represent hydrogen, optionally halogenated alkyl, alkenyl, alkynyl, alkoxyalkyl, alkylthioalkyl, or represent optionally interrupted by heteroatoms or represents aryl, aralkyl or heteroaryl optionally substituted by halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro,

or where

A and B together with the carbon atoms to which they are bound form a saturated or unsaturated ring which is optionally interrupted by heteroatoms and optionally substituted,

D represents oxygen, sulfur or -NH-,

E ⁺ stands for metal ion equivalent or ammonium ion,

L and M represent oxygen and/or sulfur,

^R represents optionally halogenated alkyl, alkenyl, alkoxyalkyl, alkylthioalkyl, polyalkoxyalkyl or cycloalkyl, which groups may be interrupted by heteroatoms, or represents optionally substituted phenyl, optionally substituted phenylalkyl, substituted heteroaryl, substituted phenoxyalkyl or substituted heteroaryloxyalkyl, and

^R represents optionally halogenated alkyl, alkenyl, alkoxyalkyl, polyalkoxyalkyl, or optionally substituted phenyl or benzyl,

R ³ , R ⁴ and R ⁵ represent independently of each other optionally halogenated alkyl, alkoxy, alkylamino, dialkylamino, alkylthio, alkenylthio, alkynylthio, cycloalkane Thio and optionally substituted phenyl, phenoxy or phenylthio,

R ⁶ and R ⁷ independently of each other represent hydrogen, optionally halogenated alkyl, alkenyl, alkoxy, alkoxyalkyl, or represent optionally substituted phenyl, or represent optionally substituted benzyl,

or ^R and ^R together represent alkenyl optionally interrupted by oxygen,

Above-mentioned formula (I) compound does not include following compound:

3-(2-methoxyphenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one,

3-(2-Chlorophenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one,

3-(2-methoxyphenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one,

3-(2-fluorophenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one.

Including the meanings of (a), (b), (c), (d), (e), (f) and (g) of the group G of the general formula (I), the following main structure (Ia )-(Ig):

Wherein A, B, D, E, L, M, X, Y, Z _n , R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ have the above-mentioned meanings.

Compounds of formula (I) or formulas (Ia) to (Ig) and their preparation are described in detail in EP-A-0528156, WO98/05638 and WO97/01535, respectively.

Among the compounds of formula (I) and their enantiomerically pure forms used with preference:

X represents C ₁ -C ₆ alkyl, halogen, C ₁ -C ₆ alkoxy or C ₁ -C ₃ -halogenated alkyl,

Y represents hydrogen, C ₁ -C ₆ alkyl, halogen, C ₁ -C ₆ alkoxy, C ₁ -C ₃ -halogenated alkyl,

Z represents C ₁ -C ₆ alkyl, halogen, C ₁ -C ₆ alkoxy,

n represents the value of 0-3,

or wherein the groups X and Z together with the phenyl to which they are bonded form a naphthyl of the formula

where Y has the above meaning,

A and B are identical or different and represent hydrogen or optionally halogenated straight-chain or branched C ₁ -C ₁₂ -alkyl, C ₃ -C ₈ -alkenyl, C ₃ -C ₈ alkyne C ₁ -C ₁₀ alkoxy-C ₂ -C ₈ alkyl, C ₁ -C ₈ polyalkoxy-C ₂ -C ₈ -alkyl, C ₁ -C ₁₀ -alkylthio-C ₂ -C ₈ -alkyl, cycloalkyl with 3-8 ring atoms which may be interrupted by oxygen and/or sulfur, or represents optionally interrupted by halogen, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - haloalkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkoxy, nitro-substituted aryl, heteroaryl or aryl-C ₁ -C ₆ -alkyl,

or where

A and B together with the carbon atoms to which they are bonded form a saturated or unsaturated 3- to 8-membered ring optionally interrupted by oxygen and/or sulfur and optionally interrupted by halogen, C ₁ -C ₆ -alkyl , C ₅ -C ₆ -alkoxy, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -haloalkoxy, C ₁ -C ₄ -alkylthio or optionally substituted aryl,

G represents hydrogen (a) or the following groups:

或    E⁺    (g)

or E ⁺ (g)

in

E ⁺ stands for metal ion equivalent or ammonium ion,

L and M represent oxygen and/or sulfur,

R ¹ represents optionally halogenated C ₁ -C ₂₀ -alkyl, C ₂ -C ₂₀ -alkenyl, C ₁ -C ₈ -alkoxy-C ₂ -C ₈ -alkyl, C ₁ -C ₈ -Alkylthio-C ₂ -C ₈ -Alkyl, C ₁ -C ₈ -Polyalkoxy-C ₂ -C ₈ -Alkyl or having 3-8 ring atoms and can be replaced by oxygen and/ Or a cycloalkyl group interrupted by sulfur atoms,

Or represents optionally substituted by halogen, nitro, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -haloalkoxy phenyl,

or represents phenyl optionally substituted by halogen, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -haloalkoxy - C ₁ -C ₆ -alkyl,

or represents heteroaryl optionally substituted by halogen and/or C ₁ -C ₆ -alkyl,

or represents phenoxy-C ₁ -C ₆ -alkyl optionally substituted by halogen and/or C ₁ -C ₆ -alkyl,

or represents heteroaryloxy-C ₁ -C ₆ -alkyl optionally substituted by halogen, amino and C ₁ -C ₆ -alkyl,

R ² represents optionally halogenated C ₁ -C ₂₀ -alkyl, C ₁ -C ₂₀ -alkenyl, C ₁ -C ₈ -alkoxy-C ₂ -C ₈ -alkyl, C ₁ -C ₈ -polyalkoxy-C ₂ -C ₈ -alkyl,

or represents phenyl or benzyl, both optionally substituted by halogen, nitro, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkyl,

R ³ , R ⁴ and R ⁵ independently of each other represent optionally halogenated C ₁ -C ₈ -alkyl, C ₁ -C ₈ -alkoxy, C ₁ -C ₈ -alkylamino, di( C ₁ -C ₈ -)alkylamino, C ₁ -C ₈ -alkylthio, C ₂ -C ₅ -alkenylthio, C ₂ -C ₅ -alkynylthio, C ₃ -C ₇ -cycloalkane Thio, or represents optionally replaced by halogen, nitro, cyano, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -halogenated alkoxy, C ₁ -C ₄ -alkylthio, C ₁ - C ₄ -haloalkylthio, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl substituted phenyl, phenoxy or phenylthio,

R ⁶ and R ⁷ independently of each other represent hydrogen, optionally halogenated C ₁ -C ₂₀ -alkyl, C ₁ -C ₂₀ -alkoxy, C ₂ -C ₈ -alkenyl, C ₁ - C ₂₀ -alkoxy-C ₁ -C ₂₀ -alkyl, or represents optionally halogenated, C ₁ -C ₂₀ -haloalkyl, C ₁ -C ₂₀ -alkyl or C ₁ -C ₂₀ -alkoxy phenyl substituted by radical, or represents benzyl optionally substituted by halogen, C ₁ -C ₂₀ -alkyl, C ₁ -C ₂₀ -haloalkyl or C ₁ -C ₂₀ -alkoxy, or together represent C ₂ -C ₆ -alkylene ring optionally interrupted by oxygen,

It does not include the following compounds:

3-(2-methoxyphenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one,

3-(2-Chlorophenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one,

3-(2-methoxyphenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one,

3-(2-fluorophenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one.

Particularly preferably used compounds of the formula (I) and in their enantiomerically pure forms:

X represents C ₁ -C ₆ -alkyl, halogen, C ₁ -C ₆ -alkoxy or C ₁ -C ₂ -haloalkyl,

Y represents hydrogen, C ₁ -C ₆ -alkyl, halogen, C ₁ -C ₆ -alkoxy, C ₁ -C ₂ -haloalkyl,

Z stands for C ₁ -C ₄ -alkyl, halogen, C ₁ -C ₄ -alkoxy,

n represents the value of 0-3,

or wherein the groups X and Z together with the phenyl to which they are bonded form a naphthyl of the formula

where Y has the above meaning,

A and B are identical or different and represent hydrogen, optionally halogenated straight-chain or branched C ₁ -C ₁₀ -alkyl, C ₃ -C ₆ -alkenyl, C ₃ -C ₆ -alkyne C ₁ -C ₈ -alkoxy-C ₂ -C 6 -alkyl _, C ₁ -C ₆ -polyalkoxy-C ₂ -C ₆ -alkyl, C ₁ -C ₆ -alkylthio -C ₂ -C ₆ -Alkyl, cycloalkyl having 3-7 ring atoms which may be interrupted by 1-2 oxygen and/or sulfur atoms, or representing optionally halogenated, C ₁ -C ₄ - Alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkoxy, nitro-substituted aryl, heteroaryl or aryl-C ₁ -C ₄ -alkyl,

or where

A and B together with the carbon atoms to which they are bonded form a saturated or unsaturated 3- to 8-membered ring which is optionally interrupted by oxygen and/or sulfur and which is optionally interrupted by halogen, C ₁ -C ₅ -alkyl, C ₁ -C ₅ -Alkoxy, C ₁ -C ₃ -Haloalkyl, C ₁ -C ₄ -Haloalkoxy, C ₁ -C ₃ -Alkylthio or optionally replaced by halogen, alkyl, alkoxy Substituted aryl substitution,

G represents hydrogen (a) or a group of the following formula:

or E ⁺ (g)

in

E ⁺ stands for metal ion equivalent or ammonium ion,

L and M are in each case oxygen and/or sulfur,

R ¹ represents optionally halogenated C ₁ -C ₁₆ -alkyl, C ₂ -C ₁₆ -alkenyl, C ₁ -C ₆ -alkoxy-C ₂ -C ₆ -alkyl, C ₁ -C ₁₆ -Alkylthio-C ₂ -C ₆ -Alkyl, C ₁ -C ₆ -Polyalkoxy-C ₂ -C ₆ -Alkyl or have 3-7 ring atoms and can be replaced by 1-2 Cycloalkyl groups interrupted by oxygen and/or sulfur atoms,

Or represents optionally substituted by halogen, nitro, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₃ -haloalkyl, C ₁ -C ₃ -haloalkoxy phenyl,

or represents phenyl-C ₁ -C ₄ -alkyl, which is optionally replaced by halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₃ -haloalkyl, C ₁ -C ₃ -haloalkoxy substituted,

or represents heteroaryl optionally substituted by halogen and/or C ₁ -C ₆ -alkyl,

or represents phenoxy-C ₁ -C ₅ -alkyl optionally substituted by halogen and C ₁ -C ₄ -alkyl,

or represents heteroaryloxy _- C ₁ -C 5 -alkyl optionally substituted by halogen, amino and C ₁ -C ₄ -alkyl,

represents optionally halogenated C ₁ -C ₁₆ -alkyl, C ₂ -C ₁₆ -alkenyl, C ₂ -C ₁₆ -alkoxy-C ₂ -C ₁₆ -alkyl, C ₁ -C ₆ -polyalkoxy-C ₂ -C ₆ -alkyl,

or represents phenyl or benzyl, both optionally substituted by halogen, nitro, C ₁ -C ₄ -alkyl, C ₁ -C ₃ -alkoxy, C ₁ -C ₃ -haloalkyl,

R ³ , R ⁴ and R ⁵ independently of each other represent optionally halogenated C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylamino, di( C ₁ -C ₆ -)alkylamino, C ₁ -C ₆ -alkylthio, C ₃ -C ₄ -alkenylthio, C ₂ -C ₄ -alkynylthio, C ₃ -C ₆ -cycloalkane Thio, or represents optionally replaced by fluorine, chlorine, bromine, nitro, cyano, C ₁ -C ₃ -alkoxy, C ₁ -C ₃ -halogenated alkoxy, C ₁ -C ₃ -alkylthio , C ₁ -C ₃ -haloalkylthio, C ₁ -C ₃ -alkyl, C ₁ -C ₃ -haloalkyl substituted phenyl, phenoxy or phenylthio,

R ⁶ and R ⁷ independently of each other represent hydrogen, optionally halogenated C ₁ -C ₂₀ -alkyl, C ₁ -C ₂₀ -alkoxy, C ₂ -C ₈ -alkenyl, C ₁ - C ₂₀ -alkoxy-C ₁ -C ₂₀ -alkyl, or represents optionally halogenated, C ₁ -C ₅ -haloalkyl, C ₁ -C ₅ -alkyl or C ₁ -C ₅ -alkoxy phenyl substituted by radical, or represents benzyl optionally substituted by halogen, C ₁ -C ₅ -alkyl, C ₁ -C ₅ -haloalkyl or C ₁ -C ₅ -alkoxy,

It does not include the following compounds:

3-(2-methoxyphenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one,

3-(2-Chlorophenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one,

3-(2-methoxyphenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one,

3-(2-fluorophenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one.

Particularly preferred compounds of formula (I) and their enantiomerically pure forms:

X represents methyl, ethyl, propyl, isopropyl, fluorine, chlorine, bromine, methoxy, ethoxy and trifluoromethyl,

Y stands for hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, fluorine, chlorine, bromine, methoxy, ethoxy and trifluoromethyl,

Z represents methyl, ethyl, isopropyl, butyl, isobutyl, tert-butyl, fluorine, chlorine, bromine, methoxy and ethoxy,

n represents the value of 0-3,

or wherein the groups X and Z together with the phenyl to which they are bound form a group of the formula

where Y has the above meaning,

A and B are identical or different and represent hydrogen, optionally halogenated straight-chain or branched C ₁ -C ₈ -alkyl, C ₃ -C ₄ -alkenyl, C ₃ -C ₄ - Alkynyl, C ₁ -C ₆ -alkoxy-C ₂ -C ₄ -alkyl, C ₁ -C ₄ -polyalkoxy-C ₂ -C ₄ -alkyl, C ₁ -C ₆ -alkylthio -C ₂ -C ₄ -alkyl, cycloalkyl having 3-6 ring atoms which may be interrupted by 1-2 oxygen and/or sulfur atoms, or representing optionally fluorine, chlorine, methyl, Ethyl, propyl, isopropyl, methoxy, ethoxy, trifluoromethyl, nitro-substituted aryl, pyridine, imidazole, pyrazole, triazole, indole, thiazole or aryl- _C1 -C ₃ -alkyl,

or where

A and B together with their bonded carbon atoms form a saturated or unsaturated three- to eight-membered ring optionally interrupted by oxygen and/or sulfur and optionally interrupted by fluorine, chlorine, C ₁ -C ₄ -alkane C ₁ -C ₄ -alkoxy, trifluoromethyl, C ₁ -C ₂ -alkylthio or aryl optionally substituted by fluorine, chlorine, bromine, methyl, methoxy,

G represents hydrogen (a) or a group of the following formula:

或    E⁺  (g)

or E ⁺ (g)

E ⁺ stands for metal ion equivalent or ammonium ion,

L and M are in each case oxygen and/or sulfur,

R ¹ represents optionally fluorinated or chlorinated C ₁ -C ₁₄ -alkyl, C ₂ -C ₁₄ -alkenyl, C ₁ -C ₄ -alkoxy-C ₂ -C ₆ -alkyl, C ₁ -C ₄ -Alkylthio-C ₂ -C ₆ -Alkyl, C ₁ -C ₄ -Polyalkoxy-C ₂ -C ₄ -Alkyl or have 3-7 ring atoms and can be 1 - cycloalkyl interrupted by 2 oxygen and/or sulfur atoms,

or represents phenyl optionally substituted by fluorine, chlorine, bromine, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, trifluoromethyl, trifluoromethoxy, nitro ,

Or represent phenyl-C ₁ -C ₃ -alkyl, which is optionally replaced by fluorine, chlorine, bromine, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, trifluoromethyl , trifluoromethoxy substituted,

or represents pyridyl, pyrimidinyl, thiazolyl and pyrazolyl, all optionally substituted by fluorine, chlorine, bromine, methyl, ethyl,

or represents phenoxy-C ₁ -C ₄ -alkyl optionally substituted by fluorine, chlorine, methyl, ethyl,

Or represent pyridyloxy-C ₁ -C ₄ -alkyl, pyrimidinyloxy-C ₁ -C ₄ -alkyl and thiazolyloxy-C ₁ -C ₅ -alkyl, all optionally replaced by fluorine, chlorine, Amino, methyl, ethyl substitution,

R ² represents optionally fluorinated or chlorinated C ₁ -C ₁₄ -alkyl, C ₂ -C ₁₄ -alkenyl, C ₁ -C ₄ -alkoxy-C ₂ -C ₆ -alkyl , C ₁ -C ₄ -polyalkoxy-C ₂ -C ₆ -alkyl,

or represents phenyl or benzyl, all optionally substituted by fluorine, chlorine, nitro, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, trifluoromethyl,

R ³ , R ⁴ and R ⁵ independently of one another represent optionally fluorinated or chlorinated C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -alkylamino , di(C ₁ -C ₄ -alkyl)-amino, C ₁ -C ₄ -alkylthio, or representatives are optionally replaced by fluorine, chlorine, bromine, nitro, cyano, C ₁ -C ₂ - Alkoxy, C ₁ -C ₄ -fluoroalkoxy, C ₁ -C ₂ -chloroalkoxy, C ₁ -C ₂ -alkylthio, C ₁ -C ₂ -fluoroalkylthio, C ₁ -C ₂ -chloroalkylthio, C ₁ -C ₃ -alkyl substituted phenyl, phenoxy or phenylthio,

R ⁶ and R ⁷ independently of each other represent C ₁ -C ₁₀ -alkyl _, C ₁ -C 10 -alkoxy, C ₁ -C ₁₀ -alkoxy, each optionally substituted by fluorine, chlorine, bromine, C ₁ -C ₁₀ -alkyl, or represents optionally substituted by fluorine, chlorine, bromine, C ₁ -C ₂₀ -haloalkyl, C ₁ -C ₂₀ -alkyl or C ₁ -C ₄ -alkoxy Phenyl, or represents benzyl optionally substituted by fluorine, chlorine, bromine, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl or C ₁ -C ₄ -alkoxy,

It does not include the following compounds:

3-(2-methoxyphenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one,

3-(2-Chlorophenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one,

3-(2-methoxyphenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one,

3-(2-fluorophenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one.

According to a preferred embodiment of the invention, dihydrofuranone derivatives, ie compounds of formula (I) in which D represents oxygen, are used. The other substituents can adopt the abovementioned meanings.

According to a further preferred embodiment of the invention, pyrrolidinedione derivatives are used, ie compounds of formula (I) in which D represents -NH-. The other substituents can adopt the abovementioned meanings.

The following special compounds for use with particular preference may be referred in particular:

Compounds of formula (Ia) mentioned in Table 1 of EP-A-528156

Compounds of formula (Ib) mentioned in Table 2 of EP-A-528156

Compounds of formula (Ic) mentioned in Table 3 of EP-A-528156

Compounds of formula (Id) mentioned in Table 4 of EP-A-528156

Compounds of formula (Ie) mentioned in Table 5 of EP-A-528156

Compounds of formula (If) mentioned in Table 6 of EP-A-528156

Compounds of formula (Ig) mentioned in Table 7 of EP-A-528156.

Other particular compounds of the formulas (Ia), (Ib), (Ic), (Id), (Ie) and (Ig) which are used with particular preference are those mentioned as preparation examples in EP-A-528156.

Other compounds of type I-1-c disclosed in WO 98/05638, especially in Examples I-1-c-1 to I-1-c-21, can be mentioned as particularly preferably used compounds.

Other compounds of type I-1-c disclosed in WO 97/01535, especially in Examples I-1-c-1 to I-1-c-9, can be mentioned as particularly preferably used compounds.

Very particularly preferably used compounds according to the invention are the following compounds A to D:

A: 3-(2,4-dichlorophenyl)-2-oxo-1-oxaspiro[4,5]dec-3-en-4-yl-butyric acid-2,2-dimethyl ester :

B: 2-oxo-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4,4]non-3-en-4-yl-3,3-dimethyl - Butyrate:

C: 3-(2,5-Dimethylphenyl)-8-methoxy-2-oxo-1-azaspiro[4,5]dec-3-en-4-yl-ethyl- Carbonate

D: 3-(4-chloro-2,5-dimethylphenyl)-8-methoxy-2-oxo-1-azaspiro[4.5]dec-3-en-4-yl-ethyl base-carbonate

The abovementioned active compounds are suitable for the systemic and/or non-systemic control of parasites which occur in domestic animals and livestock in animal husbandry and livestock breeding, as well as in zoo animals, In laboratory animals, laboratory animals and pets. In this context, the aforementioned compounds are active against all or individual developmental stages of the pests and against resistant and normally sensitive species of the pests.

Parasites especially refer to arthropods. The formulations according to the invention are preferably used for controlling ectoparasites.

The aforementioned ectoparasites include: fly ticks, soft ticks, scabies mites, lice mites, flies (biting and licking types), parasitic fly larvae, lice, head lice, bird lice and fleas.

These parasites include:

From the order of the lice, for example, the genus Hemolopus, the genus Phytognathus, the genus Pubicus, the genus Pubicidae, and the genus Peloidus.

Trichophagia and Pythias suborders and Slenderocera, e.g. Plethus genus, Pythus brevicornus, Pythias spp., Pythias genus, Werneckiella genus, Lepikentron spp, Chewing lice genus, Feline lice species belongs to.

Diptera and Longocera and Brachycera, such as Aedes, Anopheles, Culex, Gnats, Euclides, Pleurotus, Ruthia, Culicoides, Aphids, Tumorfly, Astraspermia, Mafly, Mafly, Philipomyia, Beefly, Musca, Odontida, Streptococcus, Hornfly, Molyfly, Lipomyia, Tsetse Genus, Calligraphy, Lucilia, Chrysalis, Dilfly, Sarcophagia, Cyclomysia, Derma, Gastonia, Lipopena, Lipoptena, Tick.

From the order of the Fleas, for example, the genus Ctenophora, Ctenocephalus, Osmania, Ceratophyllus.

From the order of the Heteroptera, for example, the genus Bedbug, Vertebra, Red Bru, Panstrongylus.

From the order of the Blattata, for example Blatta orientalis, Periplaneta americana, Blattella germanica, and the genus Blattata.

Acari subclasses (Acarina), and Metastigmata and Mesostigmata, for example, Acetorodicus, Adyrhynchus, Pyrocystis, Ixodes, Anthropophysis, Bovine ticks, Derma , Haemophysalis genus, Hyalomys genus, Rhizocephalus spp., Dermatophthora spp., Prickly mite spp., Pulmonary stinger genus, Chrysostomus spp., Varroa mite spp.

Acarina (former stigmata) and Acarina (aspirata), e.g. Acarina spp., Ichimangi, Avulina spp., Sarcocarpus, Pleurotus spp., Demodex spp , Chigger, Listrophorus, Acarina, Tyrophagous, Xylophilus, Hypodectes, Pteroptera, Pruritus, Chigger, Otomitus, Scabies, Scab, Pimple Acarids, Acarids, and Hymenoides.

Livestock and breeding animals include mammals such as cattle, horses, sheep, pigs, goats, camels, buffaloes, donkeys, rabbits, yellow deer, reindeer; fur animals such as mink, lizards, raccoons; such as chickens, geese, turkeys ,duck.

Laboratory and experimental animals include mice, rats, guinea pigs, golden hamsters, dogs and cats.

Pets include dogs and cats.

Prophylactic and therapeutic applications are possible.

The active compounds for systemic control of parasites are preferably administered directly or in suitable formulations enterally, parenterally, dermally or nasally, in particular orally, percutaneously, by pour-on/spot-on formulations, or It is administered as an injection.

The active compounds are administered enterally, for example orally in the form of powders, tablets, capsules, pastes, drinks, granules, oral solutions, suspensions and emulsions, boluses, medicated feed or drinking water. Transdermal administration is in the form of, for example, dipping, spraying, pouring or spotting. Parenteral administration is in the form of, for example, injections (intramuscular, subcutaneous, intravenous, intraperitoneal) or implants.

Solutions for injection are prepared by dissolving the active compound in a suitable solvent and adding auxiliary agents such as solubilizers, acids, bases, buffer salts, antioxidants, preservatives, if necessary. The solution is sterile filtered and packaged tightly.

Examples of solvents that may be mentioned are: physiologically acceptable solvents such as water, alcohols such as ethanol, butanol, benzyl alcohol, glycerol, propylene glycol, polyethylene glycol, N-methylpyrrolidone and mixtures thereof.

If desired, the active compounds can also be dissolved in physiologically acceptable vegetable or synthetic oils suitable for injection.

Solubilizers which may be mentioned are, for example, solvents which facilitate the dissolution of the active compound in the main solvent or which prevent its precipitation. Examples are polyvinylpyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan esters.

Examples of preservatives are: benzyl alcohol, chlorobutanol, parabens, n-butanol.

Formulations suitable for oral administration that may be mentioned are, for example, tablets, homogeneous solutions, emulsions, suspensions.

The oral solution is administered directly. The concentrate is first diluted to the use concentration, and then administered orally. Oral solutions and concentrates are prepared as above for injectable solutions, but the sterilization procedure may be omitted.

Formulations suitable for transdermal administration are solutions containing the active compound, if desired, with absorption enhancers, as is known. Examples of absorption enhancers are DMSO (dimethylsulfoxide), DMF (dimethylformamide), triglycerides and long-chain aliphatic fatty acid esters, azone and its derivatives, terpenes and fragrances. Essential oils, amino acid derivatives.

The formulations contain the active compound in a concentration of 0.1-65% by weight, preferably in a concentration of 1.0-40% by weight.

For the systemic control of parasites in animals, it has generally proven advantageous to administer amounts of approximately 0.5 to 100 mg of active compound/kg of body weight in order to obtain good results.

Skin administration is carried out, for example, by bathing, dipping, spraying, pouring or spotting, rinsing, shampooing, drenching, dusting, or through solid preparations.

Suitable formulations are:

Solutions or concentrates for administration in dilution, sprays for direct application, spot-on/pour-on solutions, pour-on/point-on formulations, gels;

Emulsions and suspensions and solid and semisolid preparations for dermal administration;

Preparations in which the active compound is incorporated into an ointment base or an oil-in-water or water-in-oil base;

Solutions for use on the skin are applied by dripping, smearing, rubbing into the skin, splashing, spraying, or by dipping, bathing or rinsing.

Solutions are prepared by dissolving the active compound in a suitable solvent and, if necessary, adding auxiliaries such as solubilizers, acids, bases, buffer salts, antioxidants, preservatives.

Solvents that may be mentioned are: water, alkanols, glycols, polyethylene glycol, polypropylene glycol, glycerol, aromatic alcohols such as benzyl alcohol, phenethyl alcohol, phenoxyethanol, esters such as ethyl acetate, butyl acetate, Benzyl benzoate, ethers such as alkylene glycol alkyl ethers such as dipropylene glycol monomethyl ether, diethylene glycol monobutyl ether, ketones such as acetone, methyl ethyl ketone, aromatic and/or aliphatic hydrocarbons, vegetable oils or Synthetic oil, DMF, dimethylacetamide, N-methylpyrrolidone, 2-pyrrolidone, 2-dimethyl-4-oxymethylene-1,3-dioxolane, 2-(1-nonyl )-1,3-Dioxolane, Ethylene Glycol Monoethyl Ether, Solketal, Propylene Carbonate, Propylene Glycol Diacetate, Lactic Acid.

If desired, the active compounds can also be dissolved in physiologically acceptable vegetable or synthetic oils.

Solubilizers which may be mentioned are, for example, solvents which facilitate the dissolution of the active compound in the main solvent or which prevent its precipitation. Examples are polyvinylpyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan esters.

Examples of preservatives are: benzyl alcohol, chlorobutanol, parabens, n-butanol.

When preparing solutions, it is advantageous to add thickeners. Thickeners are: inorganic thickeners such as bentonite, colloidal silicon dioxide, aluminum monostearate, organic thickeners such as cellulose derivatives, polyvinyl alcohol and its copolymers, acrylates and methacrylates.

Gels for application to or smearing onto the skin are prepared by treating a solution prepared as described above with a thickening agent in an amount sufficient to obtain a clear composition of ointment-like consistency. The thickener is the thickener described above.

Pour-on/spot-on formulations are poured, spotted or spilled onto a limited area of skin and the active compound is distributed over the body surface. Pour-on/spot-on formulations are also possible in which the active compound penetrates the skin and acts systemically.

Pour-on/spot-on formulations are prepared by dissolving, suspending or emulsifying the active compound in a suitable skin-tolerant solvent or solvent mixture. If necessary, other additives such as colorants, antioxidants, light stabilizers, thickeners can be added. In the case of systemically acting pour-on/spot-on formulations, it is advantageous to additionally add absorption promoters.

Colorants are all those which are approved for use in animals and which can be dissolved or suspended.

Other additives are spreading oils such as isopropyl myristate, dipropylene glycol nonanoate, silicone oil, fatty acid esters, triglycerides, fatty alcohols.

Antioxidants are sulfites or metabisulfites such as potassium metabisulfite, ascorbic acid, butylated hydroxytoluene, butylated hydroxyanisole, tocopherol.

Light stabilizers are, for example, benzophenones or Novantiso acids.

Examples of thickeners are cellulose derivatives, starch derivatives, polyacrylates, natural polymers such as alginates, gelatin.

Examples of absorption enhancers are DMSO, spreading oils such as isopropyl myristate, dipropylene glycol nonanoate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.

Emulsions can be administered orally, transdermally or by injection. Emulsions are either water-in-oil or oil-in-water.

Emulsions are prepared by dissolving the active compound in a hydrophobic or hydrophilic phase with the aid of suitable emulsifiers and, if necessary, other auxiliaries such as colorants, absorption accelerators, preservatives, antioxidants, light stabilizers, Tackifier, homogenize this phase with the solvent of the other phase.

The following substances can be used as the hydrophobic phase (oil): paraffin oil, silicone oil, natural vegetable oils such as sesame oil, almond oil, castor oil, synthetic triglycerides such as caprylic/capric diglycerides, vegetable oils with C ₈ - ₁₂ chain lengths Triglyceride mixtures of fatty acids or other specially selected natural fatty acids, partial glyceride mixtures of saturated or unsaturated fatty acids, if necessary also containing hydroxyl groups, mono- and diglycerides of C ₈ /C ₁₀ -fatty acids .

Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, hexyl laurate, dipropylene glycol nonanoate, medium-chain branched-chain fatty acids and chain-length C ₁₆ -C ₁₈ saturated fatty alcohols Esters, Isopropyl myristate, Isopropyl palmitate, Caprylic/capric esters of saturated fatty alcohols of chain length C ₁₂ -C ₁₈ , Isopropyl stearate, Oleyl oleate, Decyl oleate , ethyl oleate, ethyl lactate, waxy fatty acid esters such as dibutyl phthalate, diisopropyl adipate, ester mixtures related to the latter, and other fatty alcohols such as isotridecanol , 2-octyldodecanol, cetyl stearyl alcohol, oleyl alcohol.

Fatty acids such as oleic acid and mixtures thereof.

As hydrophilic phase, the following compounds may be mentioned:

Water, alcohols such as propylene glycol, glycerin, sorbitol and mixtures thereof.

As emulsifiers, the following compounds may be mentioned:

Nonionic surfactants such as polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glyceryl monostearate, polyoxyethyl stearate esters, alkylphenyl polyglycol ethers; amphoteric surfactants such as disodium N-lauryl-β-iminodipropionate or lecithin;

Anionic surfactants such as sodium lauryl sulfate, fatty alcohol ether sulfate, monoethanolamine salt of mono/dialkyl polyethylene glycol ether orthophosphate;

Cationic surfactants such as cetyltrimethylammonium chloride.

Other auxiliaries that may be mentioned are: viscosity-increasing and emulsion-stabilizing substances such as carboxymethylcellulose, methylcellulose and other cellulose and starch derivatives, polyacrylates, alginate gelatin, gum arabic, polyethylene Pyrrolidone, polyvinyl alcohol, copolymer of methyl vinyl ether and maleic anhydride, polyethylene glycol, wax, colloidal silicon dioxide, or mixtures thereof.

Suspensions can be administered orally, dermally or in the form of injections. Suspensions are prepared by suspending the active substance in a carrier liquid, if necessary using other auxiliaries such as wetting agents, colorants, absorption accelerators, preservatives, antioxidants or light stabilizers.

Carrier liquids which may be mentioned are all homogeneous solvents and solvent mixtures.

Wetting agents (dispersants) that may be mentioned are those wetting agents (dispersants) specified above.

Other auxiliaries which may be mentioned are those detailed above.

Semisolid formulations can be administered orally or dermally. They differ from the aforementioned suspensions and emulsions only by their higher viscosity.

To prepare solid preparations, the active compound is mixed with suitable carriers, if necessary using auxiliaries, and shaped as desired.

Carriers which may be mentioned are all solid inert substances which are physiologically acceptable. Can be inorganic and organic substances. Examples of inorganic substances are sodium chloride, carbonates such as calcium carbonate, bicarbonates, alumina, silicic acid, clays, precipitated or colloidal silica, phosphates.

Auxiliaries are the preservatives already mentioned above, antioxidants, colorants.

Other suitable auxiliaries are glidants and lubricants such as magnesium stearate, stearic acid, talc, bentonite.

The ready-to-use formulations contain the active compound in a concentration of 1 ppm to 80% by weight, preferably 0.01 to 65% by weight. Preferred active compound amounts are 1-50% by weight, particularly preferably 5-40% by weight.

The preparations diluted before use contain the active compound in a concentration of 0.5 to 90% by weight, preferably 1 to 50% by weight.

In general, it has proven advantageous to administer active compound in amounts of about 0.5 to about 100 mg, preferably 1 to 50 mg, per kilogram of body weight per day for effective results.

As solid preparations, mention may be made of powders, premixtures and concentrates, granules, pellets, tablets, boluses, capsules, aerosols and inhalants, and shaped articles.

In a preferred embodiment, the parasite control according to the invention is carried out non-systemically by dermal administration.

Another preferred embodiment that may be mentioned is the non-systemic administration via shaped articles. Shaped products are collars, pendants for collars, ear tags, fixing straps for limbs or body parts, adhesive tapes and adhesive films, and peelable films.

In order to achieve good results, it has proven to be advantageous to administer a solid preparation according to the invention which releases an amount of active compound of 10 mg to about 300 mg, preferably 20-200 mg, particularly preferably 25-160 mg/kg, over three weeks to be treated. Handle animal weights.

Materials suitable for the preparation of shaped articles are thermoplastic and flexible thermosetting polymers and elastomers and thermoplastic elastomers. Those that may be mentioned are polyethylene resins, polyurethanes, polyacrylates, epoxy resins, cellulose, cellulose derivatives, polyamides and polyesters, which are sufficiently compatible with the abovementioned active compounds. The polymer must have sufficient strength and flexibility to avoid tearing or shattering during molding. They must be durable enough to resist normal wear and tear. Furthermore, the polymers must enable sufficient transfer of the active compound to the surface of the shaped article.

Polyethylene resins include polyvinyl halides such as polyvinyl chloride, polyvinyl chloride/vinyl acetate, and polyvinyl fluoride; polyacrylates and polymethacrylates such as polymethyl acrylate and polymethyl methacrylate; and polyethylene Benzene such as polystyrene and polyvinyltoluene. Special mention should be made of polyvinyl chloride.

Plasticizers suitable for use in the preparation of polyethylene resin-based shaped articles are those conventionally used for plasticizing solid vinyl resins. The plasticizer used depends on the resin and the compatibility of the resin with the plasticizer. Examples of suitable plasticizers are phosphoric acid esters, and also phthalates, such as dimethyl phthalate and dioctyl phthalate, and adipate esters, such as diisobutyl adipate. Other esters such as azelate, maleate, ricinoleate, myristate, palmitate, oleate, sebacate, stearate and benzene Triesters and complexed linear polyesters, polymer plasticizers and epoxidized soybean oil. The amount of plasticizer corresponds to about 10-50%, preferably about 20-45%, by weight of the total composition.

The shaped articles may additionally contain other ingredients such as stabilizers, lubricants, fillers and dyes which do not alter the essential properties of the composition. Suitable stabilizers are antioxidants and agents which protect the tape from UV rays and from undesired degradation during processing such as molding. Some stabilizers such as epoxidized soybean oil additionally act as a second plasticizer. Examples of lubricants that can be used are stearates, stearic acid and low molecular weight polyethylene. These ingredients are used in concentrations of up to about 5% by weight of the total composition.

In the production of vinyl shaped articles, the various ingredients are mixed by known methods and compression-shaped by known molding or injection molding techniques.

In principle, the choice of processing technology for producing shaped articles depends technically on the rheology of the tape material and on the desired shape of the tape. The processing can be adjusted to suit the processing technique or the nature of the forming. Processes can be classified in terms of processing technology according to the rheological regimes they undergo. Thus, casting, pressing, injection molding and coating are possible for various tape materials, and injection moulding, molding, calendering, grinding and bending edges where necessary may be suitable for elasto-viscous polymers. Classified according to the nature of the forming, the shaped articles of the present invention can be prepared by casting, dipping, pressing, injection molding, molding, calendering, embossing, bending, thermoforming, and the like.

These processing techniques are known and need not be explained in more detail. In principle, what has been said above using polyethylene resins as an example also applies to other polymers.

The polyurethane used as carrier material is produced in a manner known per se, namely by combining polyisocyanates with high molecular weight compounds having at least two isocyanate-reactive groups and optionally low molecular weight chain extenders and/or mono Functional chain terminator reaction.

For this purpose, use the following:

Polyisocyanates with isocyanurate groups are described, for example, in US-PS3001973, DE-PS1022789, 1222067 and 1027394 and DE-OS1929034 and 2004048; polyisocyanates with urethane groups are described, for example, in DE-PS752261 or US-PS3394164; polyisocyanates with acylated urea groups, disclosed in DE-PS1230778; polyisocyanates with biuret groups, described for example in DE-PS1101394, US-PS3124605 and 3201372 and GB-PS889050; The polyisocyanate prepared by reaction is described in, for example, US-PS3654106; the polyisocyanate with ester groups is mentioned in, for example, GB-PS965474 and 1072956, US-PS3567763 and DE-PS1231688; the reaction product of the above-mentioned isocyanate and acetal is disclosed in DE-PS1072385; and polyisocyanates containing polyfatty acid residues, as described in US-PS3455883.

It is also possible to use distillation residues which have isocyanate groups and are produced in large-scale isocyanate production, if appropriate dissolved in one or more of the abovementioned polyisocyanates. Furthermore, it is also possible to use any desired mixtures of the aforementioned polyisocyanates.

Preferred polyisocyanates are generally toluene diisocyanate and diphenylmethane diisocyanate.

Polyols already containing urethane or urea groups, and optionally modified natural polyols such as castor oil, carbohydrates or starches, polyesteramides and polyamides, which include, for example, polyhydric saturated and Unsaturated carboxylic acids or their anhydrides and polybasic saturated and unsaturated aminoalcohols, diamines, polyamines and mixtures thereof produce mainly linear condensates. Adducts of alkylene oxides with phenol/formaldehyde resins or with urea/formaldehyde resins can be used according to the invention.

Representatives of these compounds are described e.g. in High Polymers, Vol. 16, "Polyurethanes, Chemistry and Technology", by Saunders-Frisch, Interscience Publishers, New York, London, Vol. 1, 1962, pp. 32-42 and 44 - 54 pages, and volume 2, 1964, pp. 5-6 and 198-199, and in "Kunststoff-Handbuch" [Plastic Handbook], vol. 7, Vieweg-Hüchtlen, Carl-Hanser-Verlag, Munich , 1966, eg pp. 45-71.

It is of course possible to use mixtures of the aforementioned compounds which have at least two isocyanate-reactive hydrogen atoms and have a molecular weight of 400 to 10,000, for example mixtures of polyethers.

When selecting high molecular weight polyol components for use in making polyurethanes, consideration must be given to the inability of the final polyurethane to swell in water. Therefore, the use of polyols having ethylene oxide units in excess (polyethylene glycol polyethers or polyesters with diethylene glycol or triethylene glycol as diol constituents) is avoided.

Thermoplastic elastomers are particularly suitable for the production of shaped articles. Thermoplastic elastomers are materials that contain a highly elastic phase in a thermoplastic processable polymer, inserted as a mixture of physical states or as chemical bonds. A classification can be made for polymer blends in which the elastomeric phase is a component of the polymeric structure. Due to the structure of thermoplastic elastomers, hard and soft regions are adjacent to each other. At this time, the hard domains form a crystalline network or a continuous phase in which the interstices are filled with elastic segments. Due to this structure, these materials have rubber-like properties.

Thermoplastic elastomers can be divided into 5 categories:

1. Copolyester

2. Polyether block amide (PEBA)

3. Thermoplastic polyurethane (TPU)

4. Thermoplastic polyolefin (TPO)

5. Styrenic block copolymers.

Suitable copolyesters (segmented polyester elastomers) are composed, for example, of a plurality of repeating short-chain ester units and long-chain ester units linked via ester linkages, wherein the short-chain ester units add up to 50% by weight of the copolyester 15-65%, and has the following formula (II)

in

R represents a divalent radical of a dicarboxylic acid having a molecular weight below about 350,

D represents a divalent radical of an organic diol having a molecular weight below about 250.

The long-chain ester units account for 35-85% of the copolyester weight in total and have the following formula (III)

in

R represents a divalent radical of a dicarboxylic acid having a molecular weight below about 350,

G represents a divalent radical of a long chain diol having an average molecular weight of about 350-6000.

The synthesis of the above copolyesters is known from DOS2239271, DOS2213128, DOS2449343 and US-P3023192.

Suitable copolyesters are available, for example, under the trade names ^_Hytrel from the company Du Pont, ^_Relpren from the company Toyobo, ^_Arnitel from the company Akzo, ^_Ectel from the company Eastman Kodak and ^_Riteflex from the company Hoechst.

Examples of suitable polyether block amides are those composed of polymer chains consisting of repeating units corresponding to formula (IV) below

in

A is a polyamide chain obtained after the polyamide having 2 terminal carboxyl groups loses the terminal carboxyl groups,

B is the polyoxyalkylene glycol chain obtained after the polyoxyalkylene glycol with terminal hydroxyl group loses the hydroxyl group,

n is the number of units forming the polymer chain.

Preferred terminal groups are hydroxyl groups or groups of compounds that interrupt polymerization.

Dicarboxylic acid polyamides having terminal carboxyl groups are obtained in a known manner, for example by polycondensation of one or more lactams and/or of one or more amino acids, also by reaction of dicarboxylic acids with diamines The polycondensation is carried out in any way in the presence of an excess of organic dicarboxylic acids, preferably having terminal carboxyl groups. During polycondensation, these carboxylic acids become constituents of the polyamide chains and, in particular, associate with the ends of the polyamide chains, resulting in ∝-ω-dicarboxylic acid polyamides. Furthermore, the dicarboxylic acid also acts as a chain terminator, which is why it is used in excess.

Polyamides can be obtained starting from lactams and/or amino acids with hydrocarbon chains of 4 to 14 carbon atoms, such as caprolactam, enantholactam, laurolactam, undecanolactam, decanolactam, 11-aminoundecalactam alkanoic acid or 12-aminododecanoic acid.

Examples that may be mentioned of polyamides obtained by polycondensation of dicarboxylic acids with diamines are the condensation products of hexamethylenediamine with adipic acid, azelaic acid, sebacic acid and 1,12-dodecanedioic acid, And the condensation product of nonanediamine and adipic acid.

Dicarboxylic acids suitable for the synthesis of polyamides, i.e. firstly in each case a carboxyl group bound to each end of the polyamide chain, and secondly dicarboxylic acids capable of acting as chain terminators are those with 4 to 20 carbon atoms, In particular alkanedicarboxylic acids such as succinic acid, adipic acid, suberic acid, azelaic acid, sebacic acid and undecanedioic acid or dodecanedioic acid, also cycloaliphatic or aromatic dicarboxylic acids Carboxylic acids such as terephthalic or isophthalic acid or cyclohexane-1,4-dicarboxylic acid.

The polyoxyalkylene glycols having terminal hydroxyl groups are unbranched or branched and have an alkylene group having at least 2 carbon atoms. Especially polyethylene glycol, polypropylene glycol and polyoxytetramethylene glycol and their copolymers.

These hydroxy-terminated polyoxyalkylene glycols have a wide range of average molecular weights; advantageously 100-6000, especially 200-3000.

The content of polyoxyalkylene glycol is 5-85% by weight, preferably 10-50%, of the total weight of polyoxyalkylene glycol and dicarboxylic acid polyamide used to prepare the PEBA polymer.

The synthesis method of the above PEBA polymer is disclosed in FR-PS7418913 (publication number 2273021), DOS2802989, DOS2837687, DOS2523991, EP-S0095893, DOS2712987 and DOS2716004.

Preferred suitable PEBA polymers are those having a random structure other than those described above. Suitable and preferably suitable PEBA polymers are known under the trade names ^_PEBAX from the company Atochem, ^_Vestamid from the company Hüls AG, ^_Grilamid from the company EMS-Chemie and ^_Kellaflex from the company DSM.

Applications can be prophylactic and therapeutic.

The active compound concentration is preferably 1-50% for collars; 2.5-35% for tags, pendants and ear tags, and 0.1-15% for films, adhesive tapes.

The novel formulations may additionally contain other active compounds such as insecticides, sex attractants, chemical infertility agents, bactericides, acaricides, nematicides, fungicides and the like. Insecticides include, for example, phosphates, carbamates, carboxylates, chlorinated hydrocarbons, phenylureas, substances produced by microorganisms, and the like.

The active compounds mentioned above can be present in liquid, solid preparations and shaped articles in admixture with synergists or other active compounds. Active compounds include insecticides such as phosphorus compounds, ie phosphates or phosphonates, natural or synthetic pyrethroids, carbamates, amidines, juvenile hormones and synthetic juvenile hormone analog active compounds.

Phosphate or phosphonate esters include:

O-Ethyl-O-(8-quinolyl)phenylphosphorothioate (quinaflu),

O, O-diethyl-O-(3-chloro-4-methyl-7-coumarinyl) phosphorothioate (masphos),

O,O-Diethyl-O-phenylglyoxyl nitrile oxime phosphorothioate (phoxim),

O,O-diethyl-O-cyanochlorobenzaldoxime phosphorothioate (chlorophom),

O, O-diethyl-O-(4-bromo-2,5-dichlorophenyl)-phosphorothioate (ethyl bromathion),

O,O,O',O'-tetraethyl-S,S'-methylene-bis(phosphorodithioate)(ethion),

2,3-p-dioxanedithiol-S,S-bis(O,O-diethylphosphorodithioate),

2-Chloro-1-(2,4-dichlorophenyl)-vinyl diethyl phosphate (chlorpyrid),

O,O-Dimethyl-O-(3-methyl-4-methylthiophenyl)thiocarbonyl phosphate (fenthion).

Carbamates include:

2-Isopropoxyphenylmethylcarbamate (propoxur),

1-Naphthyl-N-methylcarbamate (Carbaryl).

Synthetic pyrethroids include compounds of formula I:

in

R ^{and R} represent halogen, optionally halogenated alkyl, optionally halogenated phenyl,

R ³ represents hydrogen or CN,

R ⁴ represents hydrogen or halogen,

R ⁵ represents hydrogen or halogen.

Among the preferred synthetic pyrethroids of formula I:

^R represents halogen, especially fluorine, chlorine or bromine,

^R represents halogen, especially fluorine, chlorine, bromine, trihalomethyl, phenyl, chlorophenyl,

R ³ represents hydrogen or CN,

R ⁴ represents hydrogen or fluorine,

R ⁵ represents hydrogen.

Among the particularly preferred synthetic pyrethroids of formula I:

R ¹ is chlorine,

^R is chlorine, trifluoromethyl, p-chlorophenyl,

R ³ stands for CN,

R ⁴ represents hydrogen or fluorine,

R ⁵ represents hydrogen.

Among the compounds of formula I to be mentioned in particular:

R ¹ represents chlorine,

R ² represents chlorine or p-chlorophenyl,

R ³ stands for CN,

R ⁴ represents fluorine at position 4,

R ⁵ represents hydrogen.

Compounds that may be mentioned individually are:

3-[2-(4-Chlorophenyl)-2-chlorovinyl]-2,2-dimethylcyclopropanecarboxylic acid (∝-cyano-4-fluoro-3-phenoxy)benzyl ester (fluthrin),

2,2-Dimethyl-3-(2,2-dichlorovinyl)-cyclopropanecarboxylic acid-∝-cyano-(4-fluoro-3-phenoxy)benzyl ester (cyfluthrin) and its enantiomers and stereoisomers,

∝-cyano-3-phenoxybenzyl (±)-cis, trans-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (deltamethrin ester),

2,2-Dimethyl-3-(2,2-dichlorovinyl)cyclopropanecarboxylic acid-∝-cyano-3-phenoxybenzyl ester (cypermethrin),

3-phenoxybenzyl (±)-cis, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (permethrin),

∝-(p-chloro-phenyl)isovaleric acid-∝-cyano-3-phenoxybenzyl ester (fenvalerate),

2-Cyano-3-phenoxybenzyl-2-(2-chloro-∝,∝,∝-trifluoro-p-toluidineamino)-3-methylbutyrate (fluvalinate) .

Amidines include:

3-methyl-2-[2,4-dimethylphenylimino]thiazoline,

2-(4-Chloro-2-methylphenylimino)-3-methylthiazolidine,

2-(4-Chloro-2-methylphenylimino)-3-(isobut-1-enyl)thiazolidine,

1,5-bis(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene (bisformamidine).

Juvenile hormones or juvenile hormone analogs include substituted diaryl ethers, benzoylureas and triazine derivatives. Juvenile hormones and juvenile hormone analogs specifically include compounds of the formula:

Substituted diaryl ethers specifically include substituted alkoxydiphenyl ethers or alkoxydiphenylmethanes of the general formula I:

in

R ¹ represents hydrogen, halogen, alkyl, alkoxy, alkylthio, haloalkyl, haloalkoxy, haloalkylthio, dioxyalkylene, dioxyhaloalkylene, CN, NO ₂ , alkenes radical, alkynyl, alkoxyalkyl, alkoxyalkoxy, hydroxyalkoxy,

R ² represents the group mentioned in R ¹ ,

R ³ represents the group mentioned in R ¹ ,

R ⁴ represents hydrogen, alkyl, haloalkyl or halogen,

R ⁵ represents the group mentioned in R ⁴ ,

Het represents an optionally substituted heteroaryl which is bonded to the residue of the radical without a heteroatom,

X, Y independently of each other represent -O-, -S-,

Z stands for -O-, -S-, -CH ₂ -, -CHCH ₃ -, -C(CH ₃ ) ₂ -,

m and n represent 0, 1, 2, 3 independently of each other, but the total number thereof is equal to or greater than 2.

Among particularly preferred compounds of formula I:

^R represents hydrogen, methyl, trifluoromethyl, methoxy, trifluoromethoxy, chlorine, fluorine,

^R2 represents hydrogen,

R ³ represents hydrogen, fluorine, chlorine, methyl,

R ⁴ represents hydrogen or methyl,

^R represents methyl, ethyl, trifluoromethyl or hydrogen,

Het represents pyridyl or pyridazinyl, which is optionally substituted by fluorine, chlorine, methyl, _NO2 , methoxy, methylmercapto,

X stands for O,

Y stands for O,

Z represents O, CH ₂ or -(CH ₃ ) ₂ -,

m stands for 1,

n stands for 1.

The following compounds are to be mentioned individually:

R ¹ R ³ R ⁵ R ⁶ Z h h _CH3 H o h h _CH3 2-Cl o 5-F h _CH3 H o h h CF ₃ H o h h C ₂ H ₅ H o h h h H o h h _CH3 H CH ₂ h h _CH3 H C(CH ₃ ) ₂

Benzoylureas include compounds of general formula (V):

in:

R ¹ represents halogen,

R ² represents hydrogen or halogen,

R ³ represents hydrogen, halogen or C _1-4 alkyl,

R ⁴ represents halogen, 1-5-halo-C _1-4 -alkyl, C _1-4 -alkoxy, 1-5-halo-C _1-4 -alkoxy, C _1-4- Alkylthio, 1-5-halo-C _1-4 alkylthio, phenoxy or pyridyloxy, all of which can optionally be replaced by halogen, C _1-4 -alkyl, 1-5 -Halo-C _1-4 -alkyl, C _1-4 -alkoxy, 1-5-halo-C _1-4 alkoxy, C _1-4 -alkylthio, 1-5-halogen Substituted by -C _1-4 -alkylthio. Particular mention should be made of the following compounds:

In each case, the combined active compound concentration and synergist concentration can be varied within a wide range of 0.1 to 25% by weight, preferably 1 to 10% by weight.

Other substances which have attracted attention with regard to their activity against parasitic protozoa are: mixtures or combinations of compounds of the formula (I) with polyether antibiotics or synthetic coccidial inhibitors.

Synthetic coccidial inhibitors or polyether antibiotics which are preferably mentioned for use in the mixtures according to the invention are:

Amprolium, sometimes in combination with a folate antagonist

Chlorhexidine

Baiqiuqing

monensin

Salt toxin

Maduramycin

Lassalin

Naramycin

Sanduramycin.

Preferred on this list are monensin, halotoxin and maduramycin. The mixture with maduramycin is especially important.

The ready-to-use formulations contain the active compound in a concentration of 10 ppm to 20% by weight, preferably 0.1 to 10% by weight.

The preparations diluted before use contain the active compound in a concentration of 0.5-90% by weight, preferably 1-50% by weight.

In general, administrations of about 0.5 to about 50 mg, preferably 1 to 20 mg, of active compound per kilogram of body weight per day have proven to be advantageous in order to obtain effective results.

In mixtures with other coccidial inhibitors or polyether antibiotics, the ratio of the active compound of the invention to other coccidial inhibitors or polyether antibiotics is 1:0.1-10 to 1:1-10. The ratio of 1:5 is preferred.

The active compounds can also be administered with the feed or drinking water of the animals.

Feed and foodstuffs contain 0.01-250 ppm, preferably 0.5-100 ppm, of active compound in combination with suitable edible substances.

The above-mentioned feeds and foodstuffs can be used for both therapeutic and prophylactic purposes.

The above-mentioned feed and foodstuffs are prepared by mixing the concentrate or premix containing 0.5-30% by weight, preferably 1-20% by weight, of the active compound mixed with edible organic or inorganic carriers with conventional feed. Edible carriers are, for example, corn flour or corn and soybean flour or mineral salts, preferably with a small amount of edible anti-dust oils (Staubverhüntungs_l), such as corn oil or soybean oil. The resulting premix is then added to the complete feed before feeding the feed to the animals.

Examples that may be mentioned are the use in coccidiosis:

For example, for the treatment and prophylaxis of coccidiosis in poultry, especially chickens, ducks, geese and turkeys, 0.1-100 ppm, preferably 0.5-100 ppm, of the active compounds are mixed with suitable edible substances such as nutrient feed. These amounts can be increased if desired, especially when the active compound is well tolerated by the recipients. Similarly, administration can be done via drinking water.

For the treatment of individual animals, for example in the treatment of coccidiosis or toxoplasmosis in mammals, the active compound is preferably administered in an amount of 0.5-100 mg/kg body weight per day in order to achieve the desired result. However, it is sometimes necessary to deviate from the above-mentioned dosages, especially according to the body weight of the patient or the route of administration, as well as due to the species of the animal and its individual response to the type of active compound or preparation and the time or interval of administration. It is therefore sometimes sufficient to use less than the aforementioned minimum amounts, while in other cases the aforementioned upper limits have to be exceeded. When administering large doses, it is advantageous to divide the administered dose into multiple single doses throughout the day.

The activity of the compounds according to the invention can be demonstrated, for example, in cage experiments using the experimental apparatus described below, in which animals are treated with the single ingredients and mixtures of the single ingredients.

Feeds containing the active compounds are prepared by intimately mixing the necessary amounts of the active compounds with a nutritionally balanced animal feed, for example together with the chicken feed detailed below.

If concentrates or premixes are to be prepared for final dilution in the feed to the values stated in the experiments, the active compound is usually mixed with an edible organic or inorganic carrier in an amount of generally about 1-30% by weight, preferably about 10-20% by weight, Such carriers are, for example, corn and soybean meal or natural salts with small amounts of edible anti-dust oils such as corn oil or soybean oil. The resulting premix is then added to complete poultry feed before the feed is fed to the animals.

Examples of the substances according to the invention for use in poultry feed are the following compositions.

52.00% roughage flour, ie: 40% corn, 12% wheat

17.00% Refined soy flour

5.00% corn gluten flour

5.00% Feed wheat flour

3.00% fishmeal

3.00% mineral blend

3.00% Alfalfa Meal

2.50% vitamin premix

2.00% crushed malt

2.00% soybean oil

2.00% meat and bone meal

1.50% whey powder

1.00% molasses

1.00% brewer's yeast combined spent brewer's grain

100.00%

The above feed contained 18% crude protein, 5% crude fiber, 1% calcium, 0.7% phosphorus and 1200i.E. of vitamin A, 1200i.E. of vitamin D3, 10mg of vitamin E, 20mg of bacitracin zinc per kg.

For example 1-20 ppm (w/w) of active compound is mixed with this feed. Suitable doses of active compound are eg 1 ppm; 2.5 ppm; 5 ppm (in each case "(w/w)" in parts by weight).

In the following examples, compounds A and B were used as active compounds.

Example

Example 1

Tested with resistant monohost cattle tick/SP resistant Parkhurst strain

Injection method

Experimental animal: adult engorged female tick (SP resistant Parkhurst strain)

Solvent: dimethyl sulfoxide

20 mg of active compound were dissolved in 1 ml of dimethylsulfoxide and lower concentrations were prepared by dilution with the same solvent.

The experiment was performed in five repetitions. 1 μl of the solution was injected into the abdomen and the animals were transferred to dishes and stored in a controlled environment room. After 7 days, the activity detection of fertilized eggs was carried out. Fertile eggs that are not visible from the outside are stored in glass test tubes in a controlled environment cabinet until approximately 24 hours later when the larvae hatch. 100% activity means that the tick did not lay fertilized eggs.

Examples of formulations such as the following compounds showed good activity in this test:

Compound A, with an amount of 100 μg, showed 100% activity (inhibition of fertilized eggs)

Compound B, at a dose of 20 μg, showed 100% activity (inhibition of fertilized egg laying).

Example 2

Testing the development of housefly larvae on cow dung after oral treatment of cattle with a preparation containing the active compound (feeding test)

Cattle weighing 300 kg are fed 3 g of the capsule formulation of active compound for three consecutive days. Fecal samples from treated animals were inoculated with 1 instar houseflies, and their development into adult flies was monitored in comparison to development on fecal samples of untreated controls. Those substances which did prevent the development of adults within 4 weeks were evaluated as effective.

Compound A showed 50% activity up to 3 days after treatment and 100% long-term activity thereafter.

Claims (2)

1. the application of the phenyl ketone-enol derivatives of general formula (I) and its enantiomerically pure form in the preparation of the medicine for preventing and treating parasites in animals and their environment, in X represents alkyl, halogen, alkoxy or haloalkyl, Y represents hydrogen, alkyl, halogen, alkoxy, haloalkyl, Z represents alkyl, halogen, alkoxy, n represents a value from 0 to 3, or the groups X and Z together with the phenyl to which they are bonded form a naphthyl of the formula where Y has the above meaning, G represents hydrogen (a) or the following groups: -CO-R ¹ (b)

-SO ₂ -R ³ (d)

or E ⁺ (g) A and B may be the same or different and represent hydrogen, optionally halogenated alkyl, alkenyl, alkynyl, alkoxyalkyl, alkylthioalkyl, or represent optionally interrupted by heteroatoms or represents aryl, aralkyl or heteroaryl optionally substituted by halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro, or where A and B together with the carbon atoms to which they are bound form a saturated or unsaturated ring which is optionally interrupted by heteroatoms and optionally substituted, D represents oxygen, sulfur or -NH-, E ⁺ stands for metal ion equivalent or ammonium ion, L and M represent oxygen and/or sulfur, ^R represents optionally halogenated alkyl, alkenyl, alkoxyalkyl, alkylthioalkyl, polyalkoxyalkyl or cycloalkyl, which groups may be interrupted by heteroatoms, or represents optionally substituted phenyl, optionally substituted phenylalkyl, substituted heteroaryl, substituted phenoxyalkyl or substituted heteroaryloxyalkyl, and ^R represents optionally halogenated alkyl, alkenyl, alkoxyalkyl, polyalkoxyalkyl, or optionally substituted phenyl or benzyl, R ³ , R ⁴ and R ⁵ represent independently of each other optionally halogenated alkyl, alkoxy, alkylamino, dialkylamino, alkylthio, alkenylthio, alkynylthio, cycloalkane Thio and optionally substituted phenyl, phenoxy or phenylthio, R ⁶ and R ⁷ independently of each other represent hydrogen, optionally halogenated alkyl, alkenyl, alkoxy, alkoxyalkyl, or represent optionally substituted phenyl, or represent optionally substituted benzyl, or ^R and ^R together represent alkenyl optionally interrupted by oxygen, Excludes the following compounds: 3-(2-methoxyphenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one, 3-(2-Chlorophenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one, 3-(2-methoxyphenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one, 3-(2-fluorophenyl)-4-hydroxy-Δ ³ -dihydrofuran-2-one. 2. A method of controlling parasites in animals and their environment, wherein an appropriate amount of an active compound of the formula (I) as claimed in claim 1 is administered to the animal.